The Efficacy and Safety of Plerixafor in Hematopoietic Stem Cell Mobilization in Patients with Non-Hodgkin Lymphoma, Multiple Myeloma, and Hodgkin Lymphoma Who Failed Mobilization with Granulocyte-Colony-Stimulating Factor Alone: A Single-Center Experience
CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2020; 41(04): 530-534
DOI: DOI: 10.4103/ijmpo.ijmpo_154_19
Abstract
Introduction
Plerixafor is a CXCR4 antagonist which is administered along with granulocyte-colony-stimulating factor (G-CSF) to mobilize hematopoietic stem cells in patients with Non-Hodgkin lymphoma (NHL) or multiple myeloma (MM), who failed the mobilization with G-CSF alone.
Methodology
This was a single-center, retrospective study of the efficacy of the plerixafor and G-CSF in 32 patients with NHL (n = 11), MM (n = 11), and Hodgkin lymphoma (HL) (n = 10) who failed mobilization with G-CSF alone.
Results
A median number of 1.21 × 106, 1.32 × 106, and 6.73 × 106 CD34 + cells were mobilized in patients with MM, NHL, and HL, respectively. Overall, 31 (96.8%) patients mobilized more than 2 × 106 CD34 + stem cells and 21 (33.75%) patients mobilized more than 5 × 106 CD34 + stem cells. All 32 (100%) patients underwent hematopoietic stem cell transplantation. There were no adverse drug events reported.
Conclusion
This retrospective study shows that plerixafor is an effective and safe mobilization agent in patients with NHL, MM, and HL who have failed mobilization with G-CSF alone.
Keywords
Hematopoietic stem cell transplantation - multiple myeloma - Non-Hodgkin lymphoma - plerixaforPublication History
Received: 17 July 2019
Accepted: 24 October 2019
Article published online:
17 May 2021
© 2020. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)
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Abstract
Introduction
Plerixafor is a CXCR4 antagonist which is administered along with granulocyte-colony-stimulating factor (G-CSF) to mobilize hematopoietic stem cells in patients with Non-Hodgkin lymphoma (NHL) or multiple myeloma (MM), who failed the mobilization with G-CSF alone.
Methodology
This was a single-center, retrospective study of the efficacy of the plerixafor and G-CSF in 32 patients with NHL (n = 11), MM (n = 11), and Hodgkin lymphoma (HL) (n = 10) who failed mobilization with G-CSF alone.
Results
A median number of 1.21 × 106, 1.32 × 106, and 6.73 × 106 CD34 + cells were mobilized in patients with MM, NHL, and HL, respectively. Overall, 31 (96.8%) patients mobilized more than 2 × 106 CD34 + stem cells and 21 (33.75%) patients mobilized more than 5 × 106 CD34 + stem cells. All 32 (100%) patients underwent hematopoietic stem cell transplantation. There were no adverse drug events reported.
Conclusion
This retrospective study shows that plerixafor is an effective and safe mobilization agent in patients with NHL, MM, and HL who have failed mobilization with G-CSF alone.
Keywords
Hematopoietic stem cell transplantation - multiple myeloma - Non-Hodgkin lymphoma - plerixaforIntroduction
High-dose chemotherapy combined with autologous hematopoietic stem cell transplantation (auto-HSCT) is the standard of care for patients with relapsed or chemosensitive non-Hodgkin lymphoma (NHL) and multiple myeloma (MM).[1],[2],[3]
Auto-HSCT improves hematologic recovery in patients by reconstituting hematopoiesis following high-dose chemotherapy.[3] In patients with relapsed or chemosensitive NHL, high-dose chemotherapy with auto-HSCT has been shown to increase disease-free survival, whereas in MM, a combination of high-dose chemotherapy with auto-HSCT improves progression-free survival and overall survival (OS).[4],[5],[6] In some situations, auto-HSCT is potentially curative.[7]
Employing an effective stem cell mobilization regimen plays a critical role in auto-HSCT. The minimum number of cells generally acceptable for transplantation is ≥2 × 106 CD34 + cells/kg.[8] Transplanting fewer than this number of cells may result in delayed engraftment of both platelets and neutrophils.[9] The target number of cells for a single transplant was defined by Weaver et al. [10] as ≥5 × 106 CD34 + cells/kg, which is important for short-term outcomes, resulting in earlier and more consistent neutrophil, and especially platelet engraftment compared with transplants with lower cell doses.[11] In some studies, transplant doses of ≥5 × 106 CD34 + cells/kg have been associated with longer disease-free survival, and OS compared with lower transplant doses.[12],[13] Obtaining a sufficient quantity of cells for auto-HSCT is difficult in approximately 20%–25%-of patients.[14],[15],[16]
Until recently, there were two main approaches to stem cell mobilization that involved the use of growth factors, such as granulocyte-colony-stimulating factor (G-CSF) alone (G) or in conjunction with chemotherapy. The administration of chemotherapy before the use of G-CSF produces a higher yield of stem cells for autologous transplantation, but this is not effective for all patients. Around 5%–40%-of patients fail to mobilize an adequate number of CD34 + cells with commonly used regimens.[17] These include patients with NHL, elderly patients[18] who are heavily pretreated,[19],[20],[21] and patients with MM who previously received multiple cycles of lenalidomide or underwent auto-HSCT.[22] Many patients with Hodgkin lymphoma (HL) who have received extensive cytotoxic chemotherapy previously will turn out to be poor-mobilizers.[23]
Advancements in HL therapy have been documented since the introduction of combination chemotherapy protocols and changes in irradiation strategies. Despite these advancements, approximately 10%-of HL patients remain refractory to these treatments in whom auto-HSCT remains one of the most important alternative treatment modalities.[24]
Plerixafor is an additional option for use in auto-HSCT. G-CSF with plerixafor augments the mobilization of CD34 + cells, particularly in patients who are considered poor mobilizers.[25],[26],[27]
Plerixafor, a bicyclam derivative, is a small molecule which selectively and reversibly antagonizes the CXCR4 chemokine receptor and blocks binding to its cognate ligand, stromal cell-derived factor-1a (SDF-1a). The interruption of the CXCR4/SDF-1a interaction results in mobilization of CD34 + cells to the peripheral blood, where they can be collected for auto-HSCT.[28] The stem cells mobilized by the combination of G-CSF plus plerixafor have been shown to differ from those mobilized by G-CSF alone, with a higher proportion of cells in the growth phase, higher numbers of B- and T-lymphocytes, natural killer cells, dendritic cells, and primitive CD34+ cells.[29],[30],[31],[32]
Methodology
This was a retrospective study conducted at HCG Cancer Centre, Bengaluru. The patients' data were retrieved from the medical records from January 2017 to October 2018.
The following data were extracted: baseline characteristics, diagnosis, CD34+ cell counts after plerixafor administration, and adverse events (if any). All patients' data were transcribed onto the case report form maintaining patient anonymity.
The patients included were based on the following inclusion criteria: (1) age 18–78 years; (2) candidates to autologous stem cell transplantation (auto-SCT) for MM, NHL, or HL; (3) who had failed to collect a minimum of 2 × 106 CD 34+ cells/kg or did not even proceed to apheresis based on a low peripheral blood CD34+ count with mobilization with G-CSF; (4) adequate organ function to undergo apheresis and transplantation; and (5) Eastern Cooperative Oncology Group Performance Status 0–2.
Exclusion criteria included: (1) diagnosis of any form of acute or chronic leukemia (including plasma cell leukemia) or myelodysplastic syndrome; (2) comorbid conditions which render the patient at high risk from treatment complications; (3) vasculitis or autoimmune disorders; (4) brain metastases, carcinomatous meningitis, or any other malignancy unless the patient had been disease-free for at least 5 years after curative intent therapy; and (5) clinically significant heart disease.
Each patient's mobilization regimen was determined by the bone marrow transplant physician. Patients received G-CSF as per the standard protocol, typically as a 10 mg/kg daily s.c. injection each morning for 4 consecutive days. From the evening of the 4th day, patients received a single injection of s.c. plerixafor at the dose of 0.24 mg/kg, administered at least 11 h prior to the following day's apheresis schedule. On the morning of the 5th day, G-CSF was administered, and apheresis began at approximately 10–12 h after plerixafor and at 1 h after G-CSF administration. The administration of plerixafor + G-CSF and apheresis was repeated daily until the collection target was achieved (sufficient cells for auto-SCT [minimum 2 × 106/kg]) or up to a maximum of four doses of plerixafor was given in total or the patient had failed to mobilize enough peripheral blood stem cells to warrant continuation. The number of CD34+ cells collected during each apheresis session was recorded. Descriptive statistics were used to analyze the data.
Results
The study included a total of 32 consecutive patients in whom the mobilization was performed using G-CSF plus plerixafor following previous mobilization failure with G-CSF alone. Patients were heavily pretreated and received a median of two lines of different chemotherapy regimen before mobilization with G-CSF plus plerixafor. The demographic, clinical characteristics, and mobilization data are summarized in [Table 1].
n (%) |
|
---|---|
MM – Multiple myeloma; HL – Hodgkin lymphoma; NHL – Non- Hodgkin lymphoma |
|
Number of patients |
32 |
Age (years), median (range) |
41.4 (21-63) |
Gender |
|
Male |
20 (45.45) |
Female |
12 (54.54) |
Primary diagnosis |
|
NHL |
11 |
MM |
11 |
HL |
10 |
Prior lines of chemotherapy, average |
2 |
Mobilization features |
MM (n=11) |
NHL (n=11) |
HL (n=10) |
---|---|---|---|
MM – Multiple myeloma; HL – Hodgkin lymphoma; NHL – Non-Hodgkin lymphoma |
|||
Cumulative CD34+ cells/kg×106 collected |
10.21 |
7.32 |
6.73 |
Median number of patients collecting minimal cell dose (≥2×106 CD34+ cells/kg) (%) |
11 (100) |
10 (90.90) |
10 (100) |
Days to collect minimal cell dose, median |
1.5 |
2 |
2.4 |
Number of patients collecting optimal cell dose (≥5×106 in NHL and≥6×106 in MM CD34+ cells/kg) (%) |
8 (72.72) |
6 (54.54) |
7 (70) |
Days to collect optimal cell dose, median |
2.5 |
2.8 |
2.8 |
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